Hwai-Chen Guo

Expertise

Structural Biology; Bioinformatics; Enzymology; Immune Responses

Research Interests

Structural Bioinformatics; Molecular Modeling; Macromolecular Crystallography; Enzymology; Immune Responses, Rare Disease.

Our laboratory is interested in the relationship of macromolecule three-dimensional structures to biochemical functions. The tools employed are X-ray crystallography and biophysics, molecular biology, protein chemistry, structural bioinformatics and modeling.

The first research area is to study enzymes involved in antigen presentation. For an epitope to be recognized by T cells, foreign antigens need to be cut into short peptides with proper sizes in order to form physical complexes with MHC molecules. A few aminopeptidases have been identified to play critical roles in trimming peptide precursors and generating the final N-termini of class I-restricted epitopes. We are pursuing structural studies on these critical enzymes.

The second research area focuses on enzymatic mechanisms, and mechanisms of protein autoproteolysis and splicing which are posttranslational processing events. We are pursuing structural studies of the autoproteolysis mechanism of glycosylasparaginase, whose mutations in humans result in an inherited lysosomal storage disorder aspartylglycosaminuria (AGU), and the autoproteolysis of a nucleoporin, Nup98, that plays important roles in the nucleocytoplasmic transport of proteins and RNAs.

The other research areas are structural studies of factors interacting with nucleic acids. These include transcription factors, regulatory proteins, reverse transcriptases, as well as restriction enzymes with unique DNA cleavage patterns. The goal is to understand the structural basis for their functions, and specific interactions of protein-protein, protein-ligand and protein-nucleic acid at atomic resolution.

Education

• Postdoctoral Fellow: Structural Biology, (1994), Harvard University - Cambridge, MA
  Supporting Area: Molecular Biology
• Ph D: Molecular Biology, (1990), Cornell University - Ithaca, NY
  Supporting Area: Chemical Engineering
  Dissertation/Thesis Title: Mutational Analysis of Transcriptional Antitermination Mediated by Lambdoid Phage Gene Q Products
• BS: Biochemistry, (1982), National Taiwan University - Taipei, Taiwan
  Supporting Area: Chemical Engineering
  Dissertation/Thesis Title:Identification of Lentinus edodes by Headspace Analysis

Biosketch

Hwai-Chen Guo is a Professor in Biological Sciences at UMass Lowell. He received his Ph.D. in Molecular Biology with a minor concentration in Chemical Engineering from Cornell University, and postdoctoral training as a Cancer Research Institute Fellow in Structural Biology at Harvard University. Guo joined the Department of Biophysics at Boston University School of Medicine as an Assistant Professor in 1994, was appointed Associate Professor in 2001, and subsequently promoted to Full Professor in 2010. He also served as a faculty member of Bioinformatics on the Charles River Campus of Boston University. In 2011, Guo accepted an offer to join the Department of Biological Sciences at UMass Lowell.

Selected Awards and Honors

• Cancer Research Institute Fellow (1991), Scholarship/Research - Cancer Research Institute
• Damon Runyon-Walter Winchell Cancer Research Fellow (1991), Scholarship/Research - Damon Runyon-Walter Winchell Cancer Research Institute
• Research Associate (1990), Scholarship/Research - Howard Hughes Medical Institute

Selected Publications

• Sui, L. and Guo, H. (2021). ERAP1 binds peptide C-termini of different sequences and/or lengths by a common recognition mechanism. Immunobiology, 226, 152112, 1-10.
• Sui, L. and Guo, H. (2021). Enhanced recombinant expression and purification of human IRAP for biochemical and crystallography studies. Biochem Biophys Rep., 27, 101042, 1-6.
• Pande, S., Guo, H. (2019). The T99K variant of glycosylasparaginase shows a new structural mechanism of the genetic disease aspartylglucosaminuria. Protein Sci.,28 1013-1023.
• Pande, S., Bizilj, W., Guo, H. (2018). Biochemical and structural insights into an allelic variant causing the lysosomal storage disorder – aspartylglucosaminuria. FEBS Letters,592 2550-2561.
• Pande, S., Lakshminarasimhan, D., Guo, H. (2017). Crystal Structure of a Mutant Glycosylasparaginase Shedding Light on Aspartylglycosaminurea-Causing Mechanism as Well as on Hydrolysis of Non-Chitobiose Substrate. Mol Genet and Metab ,121 150-156.
• Sui, L., Gandhi, A., Guo, H.F. (2016). Crystal Structure of a Polypeptide’s C-Terminus in Complex with the Regulatory Domain of ER Aminopeptidase 1. Molecular Immunology,80 41 - 49.
• Sui, L., Gandhi, A., Guo, H.F. (2015). Single-Chain Expression and Crystallization of an Antigenic C-Terminus in Complex with the Regulatory Domain of ER Aminopeptidase 1. Crystal Structure Theory and Applications ,4 47-52.
• Sui, L., Lakshminarasimhan, D., Pande, S., Guo, H. (2014). Structural Basis of a Point Mutation That Causes the Genetic Disease Aspartylglucosaminuria. Structure,22 1855-1861.
• Guo, H.F., Gandhi, A., Lakshminarasimhan, D., Sun, Y. (2011). Structural Insights into the Molecular Ruler Mechanism of the Endoplasmic Reticulum Aminopeptidase ERAP1. Sci. Rep. (Nature Publishing Group),1 186-191.
• Wang, Y., Guo, H.F. (2010). Crystallographic Snapshot of Glycosylasparaginase Precursor Poised for Autoprocessing. Journal of Molecular Biology,403 120-130.
• Sun, Y., Guo, H.F. (2008). Structural Constraints on Autoprocessing of the Human Nucleoporin Nup98. Protein Science,17 494-505.
• Wang, Y., Guo, H.F. (2007). Crystallographic Snapshot of a Productive Glycosylasparaginase-Substrate Complex. Journal of Molecular Biology,366 82-92.
• Liu, X., Olczak, T., Guo, H.F., Dixon, D.W., Genco, C.A. (2006). Identification of Amino Acid Residues Involved in Heme Binding and Hemoprotein Utilization in the Porphyromonas Gingivalis Heme Receptor. HmuR. Infect. Immun.,74 1222-1232.
• Meyer, R.D., Qian, X., Guo, H.F., Rahimi, N. (2006). Leucine Motif-dependent Tyrosine Autophosphorylation of Type III Receptor Tyrosine Kinases. Journal of Biological Chemistry,281(13) 8620-8627.
• Meng, J., Vardar, D., Wang, Y., Guo, H.F., Head, J.F., McKnight, C.J. (2005). High-Resolution Crystal Structures of Villin Headpiece and Mutants with Reduced F-Actin Binding Activity. Biochemistry,44(36) 11963-11973.
• Xu, Q.S., Roberts, R.J., Guo, H.F. (2005). Two Crystal Forms of the Restriction Enzyme Mspi-DNA Complex Show the Same Novel Structure. Protein Sci.,14 2590-2600.
• Xu, Q.S., Kucera, R.B., Roberts, R.J., Guo, H.F. (2004). An Asymmetric Complex of Restriction Endonuclease MspI on Its Palindromic DNA Recognition Site. Structure,12 1741-1747.
• Qian, X., Guan, C., Guo, H.F. (2003). A Dual Role for an Aspartic Acid in Glycosylasparaginase Autoproteolysis. Structure,11 997-1003.
• Wang, X., Qian, X., Guo, H.F., Hu, J. (2003). Heat Shock Protein 90-Independent Activation of Truncated Hepadnavirus Reverse Transcriptase. Journal of virology,77(8) 4471-4480.
• Wang, Y., Guo, H.F. (2003). Two-Step Dimerization for Autoproteolysis to Activate Glycosylasparaginase. . J. Biol. Chem.,278 3210-3219.
• Guo, H.F. (2003). Type II Restriction Endonucleases: Structures and Applications (pp. 225-245). Recent Research Developments in Macromolecules. S.G. Pandalai , ed. (Trivandrum, India: Research Signpost)
• O' Loughlin, T.J., Xu, Q., Kucera, R.B., Dorner, L.F., Sweeney, S., Schildkraut, I., Guo, H.F. (2000). Crystallization and Preliminary X-Ray Diffraction Analysis of Mspl Restriction Endonuclease in Complex with Its Cognate DNA. Acta Crystallogr. D,56 1652-1655.
• Cui, T., Liao, P., Guan, C., Guo, H.F. (1999). Purification and crystallization of precursors and autoprocessed enzymes of Flavobacterium glycosylasparaginase: an N-terminal nucleophile hydrolase. Acta Crystallogr. D,55 1961-1964.
• Xu, Q., Buckley, D., Guan, C., Guo, H.F. (1999). Structural Insights into the Mechanism of Intramolecular Proteolysis. Cell,98 651-661.
• Guo, H.F., Xu, Q., Buckley, D., Guan, C. (1998). Crystal Structures of Flavobacterium Glycosylasparaginase: An N-Terminal Nucleophile Hydrolase Activated by Intramolecular Proteolysis. J. Biol. Chem.,273 20205-20212.
• Bouvier, M., Guo, H.F., Smith, K.J., Wiley, D.C. (1998). Crystal Structures of HLA-A*0201 Complexed with Antigenic Peptides with Either the Amino- or Carboxyl-Terminal Group Substituted by a Methyl Group. Proteins Struct. Funct. Genet.,33 97-106.
• Guo, H.F., Madden, D.R., Silver, M.L., Jardetzky, T.S., Gorga, J.C., Strominger, J.L., Wiley, D.C. (1993). Comparison of the P2 Specificity Pocket in Three Human Histocompatibility Antigens: HLA-A*6801, HLA-A*0201 and HLA-B*2705. Proc. Natl. Acad. Sci. USA,90 8053-8057.
• Silver, M.L., Guo, H.F., Strominger, J.L., Wiley, D.C. (1992). Atomic Structure of a Human MHC Molecule Presenting an Influenza Virus Peptide. Nature,360 367-369.
• Guo, H.F., Jardetzky, T.S., Garrett, T.P., Lane, W.S., Strominger, J.L., Wiley, D.C. (1992). Different Length Peptides Bind to HLA-aw68 Similarly at Their Ends but Bulge out in the Middle. Nature,360 364-366.
• Guo, H.F., Kainz, M., Roberts, J.W. (1991). Characterization of the Late-Gene Regulatory Region of Phage 21. J. Bacteriology,173 1554-1560.
• Guo, H.F., Roberts, J.W. (1990). Heterogeneous Initiation Due to Slippage at the Bacteriophage 82 Late Gene Promoter in Vitro. Biochemistry,29 10702-10709.
• Goliger, J.A., Yang, X., Guo, H.F., Roberts, J.W. (1989). Early Transcribed Sequences Affect Termination Efficiency of Escherichia Coli RNA Polymerase. Journal of Molecular Biology,205 331-341.